Abstract

Sexual experience in male rodents, induced by a first exposure to a receptive female, improves efficiency of following copulations. In mice, the mechanisms supporting this improvement are poorly understood. We characterized molecular modifications of the mouse hypothalamic medial preoptic area (mPOA), the main integrative structure for male sexual behaviour, after a single mating event. This paradigm induced long-lasting behavioural improvements and mPOA morphological changes, evidenced by dendritic spine maturation and an increase in the acetylated and tri-methylated forms of histone H3. Ejaculation affected testosterone, progesterone and corticosterone levels in both naive and experienced mice, but sexual experience did not modify basal plasma or hypothalamic levels of steroids. In contrast to studies carried out in rats, no changes were observed, either in the nitrergic system, or in sex steroid receptor levels. However, levels of glutamate- and calcium-associated proteins, including PSD-95, calbindin and the GluN1 subunit of the NMDA receptor, were increased in sexually experienced male mice. The Iba-1 microglial marker was up-regulated in these animals suggesting multicellular interactions induced within the mPOA by sexual experience. In conclusion, plasticity mechanisms induced by sexual experience differ between rat and mouse, even if in both cases they converge to potentiation of the mPOA network.

Highlights

  • Male sexual behaviour is a well-conserved behaviour across several species of rodents

  • Since learning paradigms are known to induce morphological changes[13] and increase dendritic spine density in the hippocampus and cortex[14], the effects of mating and sexual experience were analysed by Golgi-Cox staining and Western blot analysis of associated pre- and post-synaptic markers: synaptotagmin, spinophilin and PSD-95, which have been demonstrated to be involved in the regulation of plasticity processes and dendritic spines stabilization[15,16,17]

  • Changes in glutamatergic neurotransmission were evaluated by Western blot analysis of proteins, such as pre-synaptic vesicular transporters vGluT1 and vGluT2, NMDA receptor subunits (GluN1, GluN2A and GluN2B), AMPA receptor subunit (GluR2) and calbindin, a dimorphic marker associated with glutamatergic transmission of unclear role in the control of sexual behavior[20]

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Summary

Introduction

Male sexual behaviour is a well-conserved behaviour across several species of rodents. Since learning paradigms are known to induce morphological changes[13] and increase dendritic spine density in the hippocampus and cortex[14], the effects of mating and sexual experience were analysed by Golgi-Cox staining and Western blot analysis of associated pre- and post-synaptic markers: synaptotagmin, spinophilin and PSD-95, which have been demonstrated to be involved in the regulation of plasticity processes and dendritic spines stabilization[15,16,17]. The level of histone H3 tri-methylated at Lys-27, methylated at Lys-5, and acetylated were investigated within the mPOA since neuroepigenetic modifications are known to be involved in learning processes[24] and to play a critical role in male sexual behaviour expression[25,26]

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